We have previously reported that the suicide inactivation of cytochrome P-450 by many structurally diverse drugs and environmental chemicals is caused by a novel pathway which involves the irreversible binding of products derived from the heme prosthetic group to the protein moiety of the enzyme. The pathway for the destruction appears to be a general one involving the initial metabolism of the chemical or drug by cytochrome P- 450 into a radical intermediate, which reacts with the heme prosthetic group, leading to its chemical activation. Most likely the reactive heme intermediate contains a radical or cationic center, which can then be attacked by an amino residue(s) of the protein moiety. If the protein is not catalytically inactivated by this first covalent event, the process can be reported until the catalytic activity of the enzyme is lost. This process may explain how other heme enzymes such as prostaglandin H synthase, prostacylin synthase, and thromboxane synthase are inactivated during their normal catalytic turnovers or by the hydroperoxides in general.